scholarly journals Cardiac Complications of Propionic and Other Inherited Organic Acidemias

2020 ◽  
Vol 7 ◽  
Author(s):  
Kyung Chan Park ◽  
Steve Krywawych ◽  
Eva Richard ◽  
Lourdes R. Desviat ◽  
Pawel Swietach
Keyword(s):  
Molecular Mechanisms ◽  
Organic Anion ◽  
Experimental Studies ◽  
Chemical Species ◽  
Propionic Acidemia ◽  
Organic Chemical ◽  
Cardiac Complications ◽  
Organic Acidemias ◽  
Clinical Observations ◽  
Experimental Findings

Clinical observations and experimental studies have determined that systemic acid-base disturbances can profoundly affect the heart. A wealth of information is available on the effects of altered pH on cardiac function but, by comparison, much less is known about the actions of the organic anions that accumulate alongside H+ ions in acidosis. In the blood and other body fluids, these organic chemical species can collectively reach concentrations of several millimolar in severe metabolic acidoses, as in the case of inherited organic acidemias, and exert powerful biological actions on the heart that are not intuitive to predict. Indeed, cardiac pathologies, such as cardiomyopathy and arrhythmia, are frequently reported in organic acidemia patients, but the underlying pathophysiological mechanisms are not well established. Research efforts in the area of organic anion physiology have increased dramatically in recent years, particularly for propionate, which accumulates in propionic acidemia, one of the commonest organic acidemias characterized by a high incidence of cardiac disease. This Review provides a comprehensive historical overview of all known organic acidemias that feature cardiac complications and a state-of-the-art overview of the cardiac sequelae observed in propionic acidemia. The article identifies the most promising candidates for molecular mechanisms that become aberrantly engaged by propionate anions (and its metabolites), and discusses how these may result in cardiac derangements in propionic acidemia. Key clinical and experimental findings are considered in the context of potential therapies in the near future.

scholarly journals Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Esther Imperlini ◽  
Lucia Santorelli ◽  
Stefania Orrù ◽  
Emanuela Scolamiero ◽  
Margherita Ruoppolo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Propionic Acidemia ◽  
Dried Blood Spots ◽  
Small Samples ◽  
Organic Acidemias ◽  
Propionate Metabolism ◽  
Economical Evaluation ◽  
Inherited Metabolic Disorders ◽  
Recent Developments

Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs.

scholarly journals Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Jesus Simal-Gandara ◽  
Dalia M. Kopustinskiene ◽  
...  
Keyword(s):  
Blood Cells ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Experimental Studies ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Current Review ◽  
Mesh Terms ◽  
Online Databases ◽  
Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

scholarly journals Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

2021 ◽  
Vol 22 (2) ◽  
pp. 660
Author(s):  
María Aguilar-Ballester ◽  
Gema Hurtado-Genovés ◽  
Alida Taberner-Cortés ◽  
Andrea Herrero-Cervera ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Leukocyte Adhesion ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Relevant Parameter

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

scholarly journals Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

2021 ◽  
Vol 7 (3) ◽  
pp. 35
Author(s):  
Go Tajima ◽  
Reiko Kagawa ◽  
Fumiaki Sakura ◽  
Akari Nakamura-Utsunomiya ◽  
Keiichi Hara ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Acid Metabolism ◽  
Neonatal Period ◽  
Propionic Acidemia ◽  
Cardiac Complications ◽  
Mild Disease ◽  
Follow Up Study ◽  
Organic Acid Metabolism ◽  
High Incidence

Propionic acidemia (PA) is a disorder of organic acid metabolism which typically presents with acute encephalopathy-like symptoms associated with metabolic acidosis and hyperammonemia during the neonatal period. The estimated incidence of symptomatic PA in Japan is 1/400,000. The introduction of neonatal screening using tandem mass spectrometry has revealed a far higher disease frequency of approximately 1/45,000 live births due to a prevalent variant of c.1304T>C (p.Y435C) in PCCB, which codes β-subunit of propionyl-CoA carboxylase. Our questionnaire-based follow-up study reveals that most of these patients remain asymptomatic. However, reports on symptomatic patients exhibiting cardiac complications such as cardiomyopathy and QT prolongation have been increasing. Moreover, there were even cases in which these cardiac complications were the only symptoms related to PA. A currently ongoing study is investigating the risk of cardiac complications in patients with neonatal screening-detected PA caused by this common variant.

scholarly journals The Influence of Alcohol Consumption on Fighting, Shoplifting and Vandalism in Young Adults

2021 ◽  
Vol 18 (7) ◽  
pp. 3509
Author(s):  
Ieuan Evans ◽  
Jon Heron ◽  
Joseph Murray ◽  
Matthew Hickman ◽  
Gemma Hammerton
Keyword(s):  
Young Adults ◽  
Longitudinal Study ◽  
Alcohol Consumption ◽  
Experimental Studies ◽  
Real Life ◽  
Self Report ◽  
Parents And Children ◽  
Experimental Findings ◽  
Avon Longitudinal Study ◽  
Causal Component

Experimental studies support the conventional belief that people behave more aggressively whilst under the influence of alcohol. To examine how these experimental findings manifest in real life situations, this study uses a method for estimating evidence for causality with observational data—‘situational decomposition’ to examine the association between alcohol consumption and crime in young adults from the Avon Longitudinal Study of Parents and Children. Self-report questionnaires were completed at age 24 years to assess typical alcohol consumption and frequency, participation in fighting, shoplifting and vandalism in the previous year, and whether these crimes were committed under the influence of alcohol. Situational decomposition compares the strength of two associations, (1) the total association between alcohol consumption and crime (sober or intoxicated) versus (2) the association between alcohol consumption and crime committed while sober. There was an association between typical alcohol consumption and total crime for fighting [OR (95% CI): 1.47 (1.29, 1.67)], shoplifting [OR (95% CI): 1.25 (1.12, 1.40)], and vandalism [OR (95% CI): 1.33 (1.12, 1.57)]. The associations for both fighting and shoplifting had a small causal component (with the association for sober crime slightly smaller than the association for total crime). However, the association for vandalism had a larger causal component.

scholarly journals Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids

2021 ◽  
Author(s):  
Daniel R. Romano ◽  
Eri Hashino ◽  
Rick F. Nelson
Keyword(s):  
Animal Models ◽  
Inner Ear ◽  
Auditory System ◽  
Hearing Aids ◽  
Molecular Mechanisms ◽  
Functional Disability ◽  
Experimental Studies ◽  
Hereditary Deafness ◽  
Human Auditory System ◽  
Human Inner Ear

AbstractSensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.

Treatment of pernicious anemia with vitamins

1927 ◽  
Vol 23 (6-7) ◽  
pp. 741-741
Author(s):  
E. Board
Keyword(s):  
Vitamin A ◽  
Pernicious Anemia ◽  
Experimental Studies ◽  
Vitamin Deficiencies ◽  
Clinical Observations

Based on both clinical observations and experimental studies, the authors attribute an important role in the origin of pernicious anemia to vitamin deficiencies in the diet, especially vitamin A.

Main approaches to treatment of hypoxia in acute respiratory distress syndrome, bacterial and viral pneumonia (part III)

2021 ◽  
pp. 38-55
Author(s):  
A. V. Vlasenko ◽  
E. A. Evdokimov ◽  
E. P. Rodionov
Keyword(s):  
Respiratory Failure ◽  
Distress Syndrome ◽  
Experimental Studies ◽  
Viral Pneumonia ◽  
Medical Technologies ◽  
Clinical Observations ◽  
Wide Range ◽  
Prevention And Treatment ◽  
High Degree

The paper summarizes data on modern approaches to the diagnosis, prevention and treatment of severe acute parenchymal respiratory failure of various origins, including ARDS due to bacterial viral pneumonia. The work is based on the data of modern well-organized studies, analysis of international clinical guidelines with a high degree of evidence, as well as the results of our own long-term experimental studies and clinical observations of the treatment of patients with ARDS of various origins, including viral pneumonia of 2009, 2016, 2020. Scientifically grounded algorithms for prevention, differential diagnosis and personalized therapy of severe acute respiratory failure using innovative medical technologies and a wide range of respiratory and adjuvant treatment methods have been formulated. The authors tried to adapt as much as possible the existing current recommendations for the daily clinical practice of anesthesiologists and resuscitators.

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